We have identified 18 genes that are required at four different steps in a genetic pathway for the development of a single type of cell the touch receptor neurons of the nematode Caenorhabditis elegans. Mutations in these genes affect either the generation of the cells, the specification of their differentiation, the maintenance of this differentiation, or cell function. The first three groups contain five genes (1in-14, 1in-32, unc- 86, mec-3, and mec-17) that appear to regulate touch cell development, and the last group (function) contains twelve genes (mec-1. 2, 4 -10, 12, 14, and 18) that are likely targets of this regulation. None of the "regulatory" genes is solely expressed in the touch cells (with the possible exception of mec-17), although some of the "function" genes are. For example, mec-3, a homeobox gene, specifies touch cell differentiation, but is expressed as well in two other pairs of neurons (the PVD and FLP cells). It is also required for its own maintained expression. The overall goal of the research proposed in this application is to exploit this developmental system to understand in molecular terms (as an extension of our genetic analysis) how the differentiation of a single type of cell is controlled by the combinatorial action of these non-cell- specific regulators. The specific aims of the proposal are: 1) To characterize the expression and function of the mec-3 gene; 2) To characterize the function of the other touch-system regulatory genes; 3) To characterize the potential target genes (the "function" class genes) involved in touch cell differentiation; 4) To identify genes required for PVD neuron function The health relatedness of this research derives from its contribution to an understanding of basic cellular and developmental control mechanisms used in higher organisms and, perhaps, man.